Pharmacokinetic/pharmacodynamics variability of echinocandins in critically ill patients: A systematic review and meta-analysis

Abstract

What is known and objective: Anidulafungin, caspofungin and micafungin are three widely used echinocandin drugs licensed for the treatment of invasive fungal infections, and their clinical use is widespread. To evaluate pharmacokinetic/pharmacodynamics variability of echinocandins in critically ill patients by comparing the differences in pharmacokinetic parameters between critically ill patients and healthy volunteers or general patients.

Methods: MEDLINE, EMBASE, The Cochrane Library and Pubmed were searched from inception until 6 September 2018. Studies investigating the pharmacokinetic parameters of echinocandins in critically ill patients, healthy volunteers or general patients were included. Our primary outcomes included AUC_{0-24 h} , C_max and C_min (24 hours). Two reviewers independently reviewed all titles, abstracts and text, and extracted data. We applied R software (R 2017) to conduct meta-analysis.

Results and discussion: Of 3235 articles screened, 17 studies were included in the data synthesis. Descriptive data from single-arm studies show that critically ill patients who received caspofungin had more stable AUC_{0-24 h} than those who received anidulafungin and micafungin. The C_max of critically ill patients who received caspofungin and micafungin was similar to healthy volunteers. However, the C_max in critically ill patients who received anidulafungin was lower than in healthy volunteers. The C_min and T_1/2 of critically ill patients who received caspofungin were larger than in healthy volunteers. The V_d and CL of critically ill patients receiving anidulafungin and micafungin were larger than in healthy volunteers.

What is new and conclusion: This systematic review provides an analysis of the pharmacokinetic/pharmacodynamics variability of echinocandins in critically ill patients. Based on the limited data available, caspofungin has less pharmacokinetic/pharmacodynamics variability than anidulafungin and micafungin.

Keywords: critically ill patients; echinocandins; pharmacokinetic/pharmacodynamics variability.